Pocock, Stuart

Abstract Introduction Cannabidiol has been shown to exert significant anti-inflammatory effects and has demonstrated efficacy in murine models of autoimmune myocarditis, pericarditis, and heart failure. The ARCHER Study assessed whether a pharmaceutically produced cannabidiol formulation showed beneficial effects on cardiac magnetic resonance (CMR) endpoints known to predict prognosis in this patient population. Methods In a multicentre international double-blind placebo-controlled phase 2 study, we randomly assigned 109 patients within 10 days of CMR confirmed diagnosis of acute myocarditis to 12 weeks of pharmaceutically produced oral cannabidiol (active) or placebo. Dose was titrated up to 10 mg/kg of body weight twice daily. Primary endpoints were the difference in extracellular volume (ECV) and global longitudinal strain (GLS) measured by CMR at week 12. Other CMR endpoints included left-ventricular ejection fraction (LVEF), LV mass, intracellular volume (ICV), LV end-diastolic and end-systolic volumes (LVEDV, LVESV), and left-atrial end-systolic volume (LAESV). Results All randomized patients (56 active/53 placebo) completed the study with no loss to follow-up. Study drug appeared safe and well tolerated. Baseline mean ECV 38.9 ± 10.9 ml, GLS −15.3 ± 3.6%, and LVEF 60.6 ± 9.9% were consistent with mild to moderate myocarditis and predominantly intact LV function. Week 12 mean ECV was 33.6 ml in the active group and 37.3 ml in the placebo group, a difference of −3.7 ml, confidence interval (CI): −7.4 to 0.1; P = .0538; GLS was −16.0% in the active group and −15.9% in the placebo group, difference of −0.1, CI: −1.2 to 1.1; P = .90. Left ventricular mass was significantly reduced in the active group at 121.1 g compared to placebo 130.3 g, a difference of −9.2, CI: −16.4 to −2.1; P = .0117. In terms of remodelling, LAESV was significantly reduced in the active group (−8.1 ml; P = .0376) while the reduction in LVEDV failed to reach significance (−7.4 ml; P = .098). Conclusion In mild-to-moderate acute myocarditis, treatment with pharmaceutically manufactured cannabidiol was not associated with a statistically significant change in myocardial ECV or GLS, although a trend towards reduction in ECV was observed. In addition, improvement in other potential markers of myocardial recovery, including a significant reduction in LV mass, was seen in the active treatment group. Further investigation of the therapeutic potential of this therapy in inflammatory cardiac conditions is warranted.

Abstract Aims More evidence is needed to quantify the association between tricuspid regurgitation (TR) and mortality in patients with heart failure (HF). Methods and results Between 2008–2017, using the Optum longitudinal database, a patient-level database that integrates multiple US-based electronic health and claim records from several health care providers, we identified 435 679 patients with new HF diagnosis and both an assessment of the left ventricular ejection fraction and at least 1 year of history. TR was graded as mild, moderate or severe and classified as prevalent (at the time of the initial HF diagnosis) or incident (subsequent new cases thereafter). For prevalent TR, the analysis was performed using a Cox proportional hazards model with adjustment for patient covariates. Incident TR was modelled as a time-updated covariate, as were other non-fatal events during follow-up. Prevalence of mild, moderate and severe TR at baseline was 10.1%, 5.1% and 1.4%, respectively. Over a median follow-up of 1.5 years, 121 273 patients (27.8%) died and prevalent TR was independently associated with survival. Compared to patients with no TR at baseline, the adjusted hazard ratios for mortality were 0.99 [95% confidence interval (CI) 0.97–1.01], 1.17 (95% CI 1.14–1.20) and 1.34 (95% CI 1.28–1.39) for mild, moderate and severe TR, respectively. In the 363 270 patients free from TR at baseline, incident TR (at least mild, at least moderate, or severe) developed during follow-up in 12.1%, 5.1% and 1.1%, respectively. Adjusted mortality hazard ratios for such new cases were 1.48 (95% CI 1.44–1.52), 1.92 (95% CI 1.86–1.99) and 2.44 (95% CI 2.32–2.57), respectively. Findings were consistent across all patient subgroups based on age, gender, rhythm, associated comorbidities, prior cardiac surgery, B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide, and left ventricular ejection fraction. Conclusions In this large contemporary patient-level database of almost half-million US patients with HF, TR was associated with a marked increases in mortality risk overall and in all subgroups. Future randomized controlled trials will evaluate the impact of TR correction on clinical outcomes and the causal relationship between TR and mortality.

Objectives: We aimed to construct a predictive model for one‐year mortality in patients undergoing invasive coronary evaluation and to examine the impact of bivalirudin on survival according to the level of baseline risk.Background: Compared to heparin plus GP IIb/IIIa inhibitors (HEP/GPI), bivalirudin decreases bleeding complications in a range of clinical presentations. The impact of preprocedural risk assessment on survival and whether this is modified by bivalirudin, has not been investigated in detail.Methods: We examined patient‐level data from the REPLACE‐2, ACUITY, and HORIZONS‐AMI trials (n = 18,819) to construct a risk‐adjusted mortality model using baseline clinical variables.Results: One‐year mortality occurred in 287 patients (3.1%) assigned to bivalirudin and 336 patients (3.6%) assigned to HEP/GPI (HR 0.85; 95% CI, 0.73–1.00; P = 0.048). Using 11 highly significant predictors of mortality, we developed an integer‐risk score to classify patients into risk tertiles. High‐risk patients had a rate of 1‐year mortality over 9‐fold greater than low‐risk patients. Consequently, the absolute mortality reduction attributed to bivalirudin was more marked in high‐risk patients: 3.1% (−0.8% to 7.0%) in the overall cohort, 4.8% (0.5% to 9.2%) in the PCI cohort (P‐interaction versus intermediate and low risk categories, 0.09 and P = 0.02, respectively).Conclusions: In patients undergoing invasive coronary evaluation, 1‐year mortality can be predicted using baseline variables. Bivalirudin treatment (versus HEP/GPI) conferred a survival benefit. © 2015 Wiley Periodicals, Inc.